Abstract:
The use of animal models continues to be essential for carrying out research into clinical phenomena, including addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate, and this may go some way to account for the apparent failures of discoveries from animal models, including the identification of potential novel therapies, to translate to the clinic. We argue here that it is overambitious and misguided in the first place to attempt to model complex, multifacetted human disorders such as addiction in animals, and especially in rodents, and that all too frequently \"validity\" of such models is limited to superficial similarities, referred to as \"face validity\", that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, a more profitable approach is to identify (a) well-defined intermediate human behavioural phenotypes that reflect defined, limited aspects of, or contributors to, the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioural phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of past and continuing weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.
摘要:
动物模型的使用对于开展临床现象的研究仍然至关重要,包括上瘾。然而,临床条件的复杂性不可避免地意味着即使是最好的动物模型也是不够的,这可能在某种程度上解释了从动物模型中发现的明显失败,包括识别潜在的新疗法,去诊所翻译.我们在这里认为,首先试图对复杂的模型进行建模是过于雄心勃勃和误导的,多层面的人类疾病,如动物成瘾,尤其是在啮齿动物中,而且这些模型的“有效性”往往仅限于表面上的相似性,称为“面部有效性”,这反映了与临床情况完全不同的潜在现象和生物过程。相反,一种更有利可图的方法是识别(A)明确定义的中间人类行为表型,有限的方面,或贡献者,人类临床疾病,和(b)开发在心理过程方面与那些离散的人类行为表型同源的动物模型,和潜在的神经生物学机制。提供了过去和持续的弱点的例子,以及对更有限的方法的建议,这些方法可以允许测试动物和人类状况之间更好的同源性。